Huafeng Wei

Publications (2)7.09 Total impact

• Article: Silencing of the TGF-β1 gene increases the immunogenicity of cells from human ovarian carcinoma.

  Huafeng Wei, Pu Liu, Elizabeth Swisher, Yuen Yee Yip, Jee Hang Tse, Kathy Agnew, Karl Erik Hellström, Ingegerd Hellström
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  ABSTRACT: Cells from many tumors produce transforming growth factor (TGF)-β which facilitates their escape from control by the immune system. We previously reported that nonimmunogenic cells from either of 2 transplantable mouse tumors became effective as therapeutic tumor vaccines after lentivirus-mediated shRNA interference to "silence" the TGF-β1 gene. We now show that cells from in vitro cultured human ovarian carcinomas (OvC) make large amounts of TGF-β1 and that this can be prevented by "silencing" the TGF-β1 gene. We further show that in vitro sensitization of peripheral blood mononuclear cells in the presence of either mitomycin-treated OvC cells whose TGF-β1 gene was silenced or in vitro matured dendritic cells that had been pulsed with homogenates from OvC cells with silenced TGF-β1 generated a stronger Th1/Tc1 immune response to the respective wild-type OvC and also to the OvC antigens mesothelin and HE4 as measured by ELIspot assays. The percentage of interferon-γ and tumor necrosis factor-α-producing CD4+ and CD8+ T cells increased while there were fewer cells expressing markers characteristic for regulatory T cells or myeloid-derived suppressor cells. Similar results were obtained when peripheral blood mononuclear cells from a patient with OvC were sensitized to dendritic cells pulsed with homogenate from autologous TGF-β1-silenced tumor cells, and a cytolytic lymphocyte response was generated to autologous OvC cells. Our results support clinical evaluation of TGF-β1-silenced tumor vaccines for immunotherapy of OvC.
  Journal of immunotherapy (Hagerstown, Md.: 1997) 04/2012; 35(3):267-75. · 3.20 Impact Factor
• Article: Elafin selectively regulates the sensitivity of ovarian cancer cells to genotoxic drug-induced apoptosis.

  Huafeng Wei, Karl Erik Hellström, Ingegerd Hellström
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  ABSTRACT: Elafin has been reported to be abundantly expressed in human epithelial ovarian carcinoma (EOC), however, its functions are poorly understood. Here, we evaluated the role of elafin in modulating the sensitivity of human EOC cells to chemotherapeutic drugs. Elafin expression was determined by ELISA in 9 established human EOC cell lines. A lentivirus encoding elafin-specific shRNA was used to down-regulate elafin expression in OVCAR3 and OV433 cells, and a plasmid encoding elafin was used to ectopically express elafin in elafin-negative SKOV3 cells. Sensitivity to cisplatin and other genotoxic agents and to paclitaxel, an inhibitor of microtubule depolymerization, was examined in OVCAR3, OV433 and SKOV3 sublines. Cell viability was determined by the MTT assay, apoptosis by annexin V/7-AAD staining and caspase activation by fluorimetric assay. Knockdown of the elafin gene decreases cisplatin IC50 by at least 2-folds in OVCAR3 and OVCAR433 cells (p<0.01) but does not affect paclitaxel IC50. The sensitivity to other genotoxic agents such as carboplatin, cyclophosphamide and 5-fluorouracil was also increased by silencing the expression of elafin. Apoptosis and caspase-3 activation were significantly augmented in cisplatin-treated OVCAR3 cells with silenced elafin. Overexpression of elafin in SKOV3 cells made them more resistant to cisplatin and decreased cisplatin-induced apoptosis and caspase activation (p<0.01). Expression of elafin decreases the sensitivity of human EOC cells to several genotoxic agents, which may have an important implication in predicting the response of patients with EOC to chemotherapy in the clinic.
  Gynecologic Oncology 03/2012; 125(3):727-33. · 3.89 Impact Factor